Anti-Inflammatory Derivatives with Dual Mechanism of Action from the Metabolomic Screening of Poincianella pluviosa.

Marisi G. Soares,João L. Baldim,Tatiane C. S. Maiolini,Olívia da S. Domingos,Danielle F. Dias,Daniela A. Chagas-Paula,Bianca G. V. Alcântara,Mário F. C. Santos,João Henrique G. Lago

doi:10.3390/molecules24234375

Abstract

Metabolomics approaches have become fundamental strategies for the analysis of complex mixtures, guiding the isolation of target compounds by focusing on unpublished or promising pharmacological properties. The discovery of novel anti-inflammatory agents is important due to several limitations regarding their potency, efficacy, and adverse effects. Thus, novel anti-inflammatory candidates are essential, aiming to find agents with better mechanisms of action. In this context, extracts from Poincianella pluviosa var. peltophoroides demonstrated significant in vivo anti-inflammatory potential. Thus, metabolomics analysis based on UHPLC-UV-HRFTMS data was performed for the identification of biomarkers with anti-inflammatory properties. Metabolomics-guided chromatographic process led to the isolation of novel compounds 4‴-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, as well as known derivatives rhuschalcone VI and caesalpinioflavone. Isolated compounds caused edema inhibition and neutrophil recruitment. Two of them showed better efficacy than reference drugs (indomethacin and dexamethasone). Results of in vivo experiments corroborated those obtained through metabolomics and statistical analyses guiding the isolation of substances of interest.

Highlights

Natural products are of great relevance for the discovery and development of new drugs due to the variety of secondary metabolites with biological importance which are biosynthesized by living organisms [1,2]
Molecules 2019, 24, 4375 requires the use of multivariate analysis for sample classification, monitoring changes in metabolite composition [4], or to determine compounds associated with pharmacological properties [5,6]
For the treatment of acute and chronic inflammation, classic nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin are widely used, which act by inhibiting the isoforms of cyclooxygenase, COX-1, and COX-2

Summary

Introduction

Natural products are of great relevance for the discovery and development of new drugs due to the variety of secondary metabolites with biological importance which are biosynthesized by living organisms [1,2]. Metabolomics, and other so-called omics sciences, such as genomics, transcriptomics, and proteomics, analyzes a biological system using the complete set of metabolites in a biological system. These strategies make it possible to detect important variables that possibly affect biological processes or activities based on metabolite-centered data [3]. Anti-inflammatory drugs are some of the most widely-used therapeutic agents in the world, since inflammation is related to several diseases resulting in pronounced morbidity. For the treatment of acute and chronic inflammation, classic nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin are widely used, which act by inhibiting the isoforms of cyclooxygenase, COX-1, and COX-2. Due to the adverse effects of COX-1 inhibition by these drugs, such as renal and gastrointestinal toxicity, selective COX-2 inhibitors have been developed [7]

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